The long-term goal of this proposed research will be the understanding of the relationship of brain MAO to the molecular mechanism of cellular aging occurring in the monoaminergic system. The oxidative deamination of neurotransmitter monoamines is now believed to be accomplished by at least two functionally different forms of monoamine oxidase, MAO-A and MAO-B with quite distinctive properties. These enzymes have been shown to increase in activity markedly in specific regions of aging brains. The first objective is to study the molecular nature of MAO-A and MAO-B in membrane-bound state. Properties such as geometry, size, polarity, proximity of the active sites will be measured with a series of active-site specific spin-labels - spin-labeled acetylenic amine of varying chain lengths. The chemical and physical properties of these molecular probes warrant its specificity of binding to the flavin cofactor and its capability of fitting inside the cavity of active sites. The second objective is to investigate the nature of the localized lipid-protein interactions which are crucial to the functional differentiation of MAO-A and MAO-B enzymes. The third objective is to establish the hypothetical regulatory mechanism of MAO-membrane system. The knowledge should be indispensable to the basic understanding of the postmaturational age-related changes in the structural and functional aspects of the multiple monoamine oxidases. The methodology and the general principle derived from the study of MAO-membrane system should contribute significantly to the science of aging in biological membranes.